WO2004022762A9 - Orthopoxvirus vectors, genes and products thereof - Google Patents
Orthopoxvirus vectors, genes and products thereofInfo
- Publication number
- WO2004022762A9 WO2004022762A9 PCT/IE2003/000120 IE0300120W WO2004022762A9 WO 2004022762 A9 WO2004022762 A9 WO 2004022762A9 IE 0300120 W IE0300120 W IE 0300120W WO 2004022762 A9 WO2004022762 A9 WO 2004022762A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- protein
- orthopoxvirus
- vector
- irak2
- inhibition
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 40
- 239000013598 vector Substances 0.000 title claims abstract description 35
- 241000700629 Orthopoxvirus Species 0.000 title claims abstract description 34
- 102220468893 Peptidyl-tRNA hydrolase ICT1, mitochondrial_A52R_mutation Human genes 0.000 claims abstract description 190
- 101100321860 Vaccinia virus (strain Copenhagen) A52R gene Proteins 0.000 claims abstract description 190
- 101100321861 Vaccinia virus (strain Western Reserve) VACWR178 gene Proteins 0.000 claims abstract description 190
- 101100161331 Variola virus (isolate Human/India/Ind3/1967) A46R gene Proteins 0.000 claims abstract description 190
- 230000011664 signaling Effects 0.000 claims abstract description 50
- 230000005764 inhibitory process Effects 0.000 claims abstract description 36
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 25
- 239000012634 fragment Substances 0.000 claims abstract description 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 17
- 206010046865 Vaccinia virus infection Diseases 0.000 claims abstract description 15
- 208000007089 vaccinia Diseases 0.000 claims abstract description 15
- 101900243365 Vaccinia virus Protein A52 Proteins 0.000 claims abstract description 6
- 102100036433 Interleukin-1 receptor-associated kinase-like 2 Human genes 0.000 claims description 62
- 101000852255 Homo sapiens Interleukin-1 receptor-associated kinase-like 2 Proteins 0.000 claims description 61
- 230000004913 activation Effects 0.000 claims description 37
- 230000000694 effects Effects 0.000 claims description 30
- 230000003993 interaction Effects 0.000 claims description 30
- 102000002689 Toll-like receptor Human genes 0.000 claims description 28
- 108020000411 Toll-like receptor Proteins 0.000 claims description 28
- 241000700605 Viruses Species 0.000 claims description 25
- 150000001413 amino acids Chemical class 0.000 claims description 19
- 230000037361 pathway Effects 0.000 claims description 19
- 239000002773 nucleotide Substances 0.000 claims description 17
- 125000003729 nucleotide group Chemical group 0.000 claims description 17
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 17
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 17
- 108020004414 DNA Proteins 0.000 claims description 15
- 239000003112 inhibitor Substances 0.000 claims description 15
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 claims description 14
- 108010067390 Viral Proteins Proteins 0.000 claims description 14
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 229960005486 vaccine Drugs 0.000 claims description 11
- 101150101278 A52R gene Proteins 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 102000003945 NF-kappa B Human genes 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 230000000840 anti-viral effect Effects 0.000 claims description 7
- 230000036039 immunity Effects 0.000 claims description 7
- 230000006870 function Effects 0.000 claims description 6
- 230000004044 response Effects 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 208000035473 Communicable disease Diseases 0.000 claims description 5
- 108010057466 NF-kappa B Proteins 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 230000019491 signal transduction Effects 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 5
- 230000003612 virological effect Effects 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 102000043136 MAP kinase family Human genes 0.000 claims description 4
- 108091054455 MAP kinase family Proteins 0.000 claims description 4
- 208000037976 chronic inflammation Diseases 0.000 claims description 4
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 238000012360 testing method Methods 0.000 claims description 4
- 125000000349 (Z)-3-carboxyprop-2-enoyl group Chemical group O=C([*])/C([H])=C([H])\C(O[H])=O 0.000 claims description 3
- 101000674731 Homo sapiens TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 Proteins 0.000 claims description 3
- 108010014632 NF-kappa B kinase Proteins 0.000 claims description 3
- 102100021228 TGF-beta-activated kinase 1 and MAP3K7-binding protein 1 Human genes 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000005847 immunogenicity Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 230000002163 immunogen Effects 0.000 claims description 2
- 230000000415 inactivating effect Effects 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 238000003780 insertion Methods 0.000 claims description 2
- 230000037431 insertion Effects 0.000 claims description 2
- 230000035772 mutation Effects 0.000 claims description 2
- 108700010766 orthopoxvirus proteins Proteins 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 230000035945 sensitivity Effects 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 230000000451 tissue damage Effects 0.000 claims description 2
- 231100000827 tissue damage Toxicity 0.000 claims description 2
- 102000003714 TNF receptor-associated factor 6 Human genes 0.000 claims 4
- 108090000009 TNF receptor-associated factor 6 Proteins 0.000 claims 4
- 101001011382 Homo sapiens Interferon regulatory factor 3 Proteins 0.000 claims 1
- 102100029843 Interferon regulatory factor 3 Human genes 0.000 claims 1
- 101001076418 Homo sapiens Interleukin-1 receptor type 1 Proteins 0.000 abstract description 2
- 102100026016 Interleukin-1 receptor type 1 Human genes 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 36
- 241000700618 Vaccinia virus Species 0.000 description 32
- 238000001994 activation Methods 0.000 description 32
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 23
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 22
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 22
- 230000006698 induction Effects 0.000 description 18
- 230000001419 dependent effect Effects 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 17
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 16
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 16
- 238000001114 immunoprecipitation Methods 0.000 description 16
- 101100512224 Dictyostelium discoideum mai gene Proteins 0.000 description 14
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 13
- 102100036073 TIR domain-containing adapter molecule 1 Human genes 0.000 description 13
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 13
- 101000595548 Homo sapiens TIR domain-containing adapter molecule 1 Proteins 0.000 description 12
- 108010002352 Interleukin-1 Proteins 0.000 description 12
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 12
- 102000000589 Interleukin-1 Human genes 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 description 9
- 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 0.000 description 9
- 108700008625 Reporter Genes Proteins 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 102000007578 Interferon Regulatory Factor-3 Human genes 0.000 description 8
- 108010032038 Interferon Regulatory Factor-3 Proteins 0.000 description 8
- 208000036142 Viral infection Diseases 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- 238000003119 immunoblot Methods 0.000 description 8
- 229920006008 lipopolysaccharide Polymers 0.000 description 8
- 230000003389 potentiating effect Effects 0.000 description 8
- 230000009385 viral infection Effects 0.000 description 8
- 241000700647 Variola virus Species 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 6
- 102100026720 Interferon beta Human genes 0.000 description 6
- 108090000467 Interferon-beta Proteins 0.000 description 6
- 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 6
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 108091008743 testicular receptors 4 Proteins 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
- 102000010170 Death domains Human genes 0.000 description 5
- 108050001718 Death domains Proteins 0.000 description 5
- 102000003810 Interleukin-18 Human genes 0.000 description 5
- 108090000171 Interleukin-18 Proteins 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000001086 cytosolic effect Effects 0.000 description 5
- 230000015788 innate immune response Effects 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 4
- 101000669406 Homo sapiens Toll-like receptor 6 Proteins 0.000 description 4
- 101000637726 Homo sapiens Toll/interleukin-1 receptor domain-containing adapter protein Proteins 0.000 description 4
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 4
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 4
- 102100039387 Toll-like receptor 6 Human genes 0.000 description 4
- 102100032120 Toll/interleukin-1 receptor domain-containing adapter protein Human genes 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 239000013613 expression plasmid Substances 0.000 description 4
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000005720 Glutathione transferase Human genes 0.000 description 3
- 108010070675 Glutathione transferase Proteins 0.000 description 3
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 108010052090 Renilla Luciferases Proteins 0.000 description 3
- 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 3
- 102100034779 TRAF family member-associated NF-kappa-B activator Human genes 0.000 description 3
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 3
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 3
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 230000001018 virulence Effects 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- OEDPHAKKZGDBEV-GFPBKZJXSA-N (2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2r)-3-[2,3-di(hexadecanoyloxy)propylsulfanyl]-2-(hexadecanoylamino)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CCCCCCCCCCCCCCC)CSCC(COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC OEDPHAKKZGDBEV-GFPBKZJXSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 101000674728 Homo sapiens TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 Proteins 0.000 description 2
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 2
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000725643 Respiratory syncytial virus Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102100021227 TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 Human genes 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 102000035181 adaptor proteins Human genes 0.000 description 2
- 108091005764 adaptor proteins Proteins 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 230000005745 host immune response Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 2
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- 102100032814 ATP-dependent zinc metalloprotease YME1L1 Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000700628 Chordopoxvirinae Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000006586 Ectromelia Diseases 0.000 description 1
- 108010040721 Flagellin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000651298 Homo sapiens TRAF-interacting protein with FHA domain-containing protein A Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 108060006678 I-kappa-B kinase Proteins 0.000 description 1
- 102000001284 I-kappa-B kinase Human genes 0.000 description 1
- 102000002227 Interferon Type I Human genes 0.000 description 1
- 108010014726 Interferon Type I Proteins 0.000 description 1
- 101710182491 Interleukin-1 receptor-associated kinase-like 2 Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 206010024503 Limb reduction defect Diseases 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 241001082241 Lythrum hyssopifolia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 101800000795 Proadrenomedullin N-20 terminal peptide Proteins 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000001203 Smallpox Diseases 0.000 description 1
- 101710157101 TIR domain-containing adapter molecule 1 Proteins 0.000 description 1
- 101710147244 TIR domain-containing protein Proteins 0.000 description 1
- 102100027651 TRAF-interacting protein with FHA domain-containing protein A Human genes 0.000 description 1
- 229940125970 Toll-Like Receptor inhibitor Drugs 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 241000870995 Variola Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000749 co-immunoprecipitation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 201000003740 cowpox Diseases 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000001378 electrochemiluminescence detection Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002621 immunoprecipitating effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000005871 monkeypox Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 108700015048 receptor decoy activity proteins Proteins 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 230000008299 viral mechanism Effects 0.000 description 1
- -1 while for TLR3 Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/275—Poxviridae, e.g. avipoxvirus
- A61K39/285—Vaccinia virus or variola virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
- G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5254—Virus avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/525—Virus
- A61K2039/5256—Virus expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24141—Use of virus, viral particle or viral elements as a vector
- C12N2710/24143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/24011—Poxviridae
- C12N2710/24111—Orthopoxvirus, e.g. vaccinia virus, variola
- C12N2710/24161—Methods of inactivation or attenuation
- C12N2710/24162—Methods of inactivation or attenuation by genetic engineering
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2003264836A AU2003264836A1 (en) | 2002-09-05 | 2003-09-05 | Orthopoxvirus vectors, genes and products thereof |
NZ538768A NZ538768A (en) | 2002-09-05 | 2003-09-05 | Orthopoxvirus vector such as vaccinia wherein the nucleotide sequence encoding A52R is inactivated by mutation or insertion of foreign DNA |
EP03794024A EP1539974A1 (en) | 2002-09-05 | 2003-09-05 | Orthopoxvirus vectors, genes and products thereof |
CA002497750A CA2497750A1 (en) | 2002-09-05 | 2003-09-05 | Orthopoxvirus vectors, genes and products thereof |
US11/071,262 US20050244430A1 (en) | 2002-09-05 | 2005-03-04 | Orthopoxvirus vectors, genes and products thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US40796502P | 2002-09-05 | 2002-09-05 | |
US60/407,965 | 2002-09-05 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/071,262 Continuation US20050244430A1 (en) | 2002-09-05 | 2005-03-04 | Orthopoxvirus vectors, genes and products thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2004022762A1 WO2004022762A1 (en) | 2004-03-18 |
WO2004022762A9 true WO2004022762A9 (en) | 2005-05-19 |
Family
ID=31978539
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IE2003/000120 WO2004022762A1 (en) | 2002-09-05 | 2003-09-05 | Orthopoxvirus vectors, genes and products thereof |
Country Status (6)
Country | Link |
---|---|
US (1) | US20050244430A1 (en) |
EP (1) | EP1539974A1 (en) |
AU (1) | AU2003264836A1 (en) |
CA (1) | CA2497750A1 (en) |
NZ (1) | NZ538768A (en) |
WO (1) | WO2004022762A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7192930B2 (en) | 2004-07-12 | 2007-03-20 | U.S. Department Of Veterans Affairs | Method and peptide for regulating cellular activity |
US20080233105A1 (en) * | 2005-09-13 | 2008-09-25 | Green William R | Compositions and methods for preventing or treating a viral infection |
US20080039395A1 (en) * | 2006-08-07 | 2008-02-14 | United States Government As Represented By The Department Of Veterans Affairs | Methods for treating septic shock |
CN102803500B (en) | 2009-06-05 | 2014-11-19 | 13治疗有限公司 | Immunoregulatory peptides and methods of use |
WO2012138879A2 (en) | 2011-04-06 | 2012-10-11 | 13Therapeutics, Inc. | Peptides for the treatment of hearing |
MX2022001870A (en) | 2019-08-14 | 2022-05-30 | Curevac Ag | Head-up display. |
-
2003
- 2003-09-05 EP EP03794024A patent/EP1539974A1/en not_active Withdrawn
- 2003-09-05 NZ NZ538768A patent/NZ538768A/en unknown
- 2003-09-05 AU AU2003264836A patent/AU2003264836A1/en not_active Abandoned
- 2003-09-05 CA CA002497750A patent/CA2497750A1/en not_active Abandoned
- 2003-09-05 WO PCT/IE2003/000120 patent/WO2004022762A1/en not_active Application Discontinuation
-
2005
- 2005-03-04 US US11/071,262 patent/US20050244430A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU2003264836A1 (en) | 2004-03-29 |
WO2004022762A1 (en) | 2004-03-18 |
NZ538768A (en) | 2007-04-27 |
EP1539974A1 (en) | 2005-06-15 |
US20050244430A1 (en) | 2005-11-03 |
CA2497750A1 (en) | 2004-03-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Volz et al. | Modified vaccinia virus Ankara: history, value in basic research, and current perspectives for vaccine development | |
Rubio et al. | Crosstalk between the type 1 interferon and nuclear factor kappa B pathways confers resistance to a lethal virus infection | |
Kerr et al. | Immune responses to myxoma virus | |
US20050244430A1 (en) | Orthopoxvirus vectors, genes and products thereof | |
Meng et al. | Identification from diverse mammalian poxviruses of host-range regulatory genes functioning equivalently to vaccinia virus C7L | |
US8961998B2 (en) | Immediate protection against pathogens via MVA | |
Zhu et al. | African swine fever virus E184L protein interacts with innate immune adaptor STING to block IFN production for viral replication and pathogenesis | |
Jentarra et al. | Vaccinia viruses with mutations in the E3L gene as potential replication-competent, attenuated vaccines: scarification vaccination | |
WO2004031225A1 (en) | Orthopoxvirus vectors, genes and products thereof | |
US20060008470A1 (en) | Use of vaccinia virus deleted for the E3L gene as a vaccine vector | |
Lynch et al. | Modified vaccinia virus Ankara can activate NF-κB transcription factors through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway during the early phase of virus replication | |
Gong et al. | A single point mutation of Ala-25 to Asp in the 14,000-Mr envelope protein of vaccinia virus induces a size change that leads to the small plaque size phenotype of the virus | |
US20090143289A1 (en) | Orthopoxvirus vectors, genes and products thereof | |
DK2635687T3 (en) | MODULE IMMUNE RESPONSES USING POXVIRUS K4 PROTEIN | |
IE20030641A1 (en) | Orthopoxvirus vectors, genes and products thereof | |
WO2004024756A2 (en) | Orthopoxvirus antigens and use thereof | |
Aricò et al. | MHV-68 producing mIFNα1 is severely attenuated in vivo and effectively protects mice against challenge with wt MHV-68 | |
EP1398380A1 (en) | Orthopoxvirus antigens and use thereof | |
Parekh | Interferons in immunity to peripheral vaccinia virus infection | |
Adams et al. | Limitations of plasmid vaccines to complex viruses: selected myxoma virus antigens as DNA vaccines were not protective | |
Sonstein et al. | TLR3 Increases Disease Morbidity and | |
Promotes | The Tanapoxvirus 15L Protein Is | |
Dai et al. | JVI Accepts, published online ahead of print on 10 August 2011 | |
Johnston | Interactions and functions of the vaccinia virus F12L protein |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2497750 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 11071262 Country of ref document: US Ref document number: 2003264836 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 538768 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2003794024 Country of ref document: EP |
|
COP | Corrected version of pamphlet |
Free format text: PAGES 1/3-3/3, SEQUENCE LISTING, ADDED |
|
WWP | Wipo information: published in national office |
Ref document number: 2003794024 Country of ref document: EP |
|
NENP | Non-entry into the national phase |
Ref country code: JP |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |